This Exploratory/Developmental Research (R21) application proposes the development of an on-chip and low cost phasing imaging microscope that can significantly simplify a broad range of existing biomedicine analysis procedures. This imaging approach, termed differential interference contrast optofluidic microscopy (DIC-OFM), will build upon our work on the optofluidic microscopy (OFM) - a high resolution, lensless and compact on-chip microscope method. Our preliminary experiments positively indicate that a low cost, simple phase imaging approach based on the use of patterned aperture clusters, that function as on-chip Young's double slit interferometers, can render differential interference contrast (DIC) microscopy type images without the use of elaborate bulk optical elements. Such an on-chip and low cost phase microscope method implies the possibility of high throughput and massively serial/parallel imaging of bio-entities. Among other uses, it can be applied in microfluidic based cell or microorganism analysis, and any other type of lab-on-a-chip applications where a compact and low cost phase imaging system is desired. We aim to demonstrate a working device that is capable of high throughput imaging with a spatial resolution of at least 1.2 micron (comparable to a 10x standard microscope) and quantitative spatial differential phase sensitivity of ~5 degree/micron. With the completion of the proposed research, we expect the technology will be sufficiently refined to be applied to tackle a wide range of basic research and biomedicine challenges. The specific aims of the proposal are as follows: 1. To construct a relay image geometry DIC-OFM prototype. 2. To construct a fully integrated DIC-OFM prototype. 3. To study and evaluate the prototypes' performance for rendering phase images of C. elegans. 4. To examine other DIC-OFM aperture configurations. The proposed research will allow us to investigate the possibility of constructing on-chip, low cost and high resolution differential interference contrast (DIC) microscopes. The propose microscope design builds upon our successful optofluidic microscope work. A compact and low cost DIC optofluidic microscope system can dramatically simplify phase imaging procedure and introduce phase imaging to a wider range of biomedical applications, which are presently hindered by the high cost of conventional DIC microscopes. [unreadable] [unreadable] [unreadable]